Viral-human chimeric transcript predisposes risk to liver cancer development and progression

Cancer Cell. 2014 Mar 17;25(3):335-49. doi: 10.1016/j.ccr.2014.01.030. Epub 2014 Feb 27.


The mutagenic effect of hepatitis B (HBV) integration in predisposing risk to hepatocellular carcinoma (HCC) remains elusive. In this study, we performed transcriptome sequencing of HBV-positive HCC cell lines and showed transcription of viral-human gene fusions from the site of genome integrations. We discovered tumor-promoting properties of a chimeric HBx-LINE1 that, intriguingly, functions as a hybrid RNA. HBx-LINE1 can be detected in 23.3% of HBV-associated HCC tumors and correlates with poorer patient survival. HBx-LINE1 transgenic mice showed heightened susceptibility to diethylnitrosamine-induced tumor formation. We further show that HBx-LINE1 expression affects β-catenin transactivity, which underlines a role in activating Wnt signaling. Thus, this study identifies a viral-human chimeric fusion transcript that functions like a long noncoding RNA to promote HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Base Sequence
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / virology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • DNA-Binding Proteins / genetics*
  • Diethylnitrosamine
  • Epithelial-Mesenchymal Transition / genetics
  • Gene Expression Profiling
  • Hepatitis B virus / genetics
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / virology
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • RNA, Long Noncoding / genetics
  • Recombinant Fusion Proteins / genetics
  • Sequence Analysis, DNA
  • Trans-Activators / genetics*
  • Transcription, Genetic / genetics
  • Transcriptional Activation / genetics
  • Transcriptome / genetics
  • Viral Fusion Proteins / genetics*
  • Viral Regulatory and Accessory Proteins
  • Wnt Proteins / metabolism
  • Wnt Signaling Pathway / genetics
  • beta Catenin / metabolism


  • DNA-Binding Proteins
  • RNA, Long Noncoding
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Viral Fusion Proteins
  • Viral Regulatory and Accessory Proteins
  • Wnt Proteins
  • beta Catenin
  • hepatitis B virus X protein
  • L1Hs-encoded protein p40, human
  • Diethylnitrosamine

Associated data

  • SRA/SRP023539